THYROID EMERGENCIES

1. Thyroid Emergencies
• Thyrotoxic Storm
• Myxedema Coma

2. Introduction
• Also known as thyrotoxic crisis, is an acute, life-threatening
complication of hyperthyroidism.
• An exaggerated presentation of thyrotoxicosis.
• sudden multisystem involvement.
• Mortality ≈ 10-75 %
• Diagnosis- clinical
• Can occur in any diagnosed/ undiagnosed case of – Graves’ disease,
TMNG, Toxic Adenoma, Iatrogenic thyrotoxicosis or any other cause
of hyperthyroidism and thyrotoxicosis

3. Epidemiology
• Rare
• It accounts for about 1% to 2% of admissions for hyperthyroidism.
US data-
• Incidence of storm is 0.57 to 0.76 cases per 100,000 per year in the normal population
• 4.8 to 5.6 cases per 100,000 per year in hospitalized patients
Japanese data-
• 0.2 per 100,000 population per year
• 0.22% of all thyrotoxicosis patients and 5.4% of hospitalized thyrotoxicosis
• M:F-1:3 same as in non thyrotoxic storm
• Average age- 43-45 years

4. Pathophysiology
• Rapid increase in thyroid hormone levels rather than the absolute hormone level –
1. Thyroid surgery
2. Following radioactive iodine t/t
3. After sudden discontinuation of the antithyroid drug
4. After administration of the large dose of iodine in contrast studies.
• Hyperactive sympathetic nervous system- acute stress or infections, causing cytokines release
and altered immunological disturbances
• The degree of thyroid hormone level is not directly related to a higher incidence of thyroid storm

5. Events Associated with the Onset of Thyrotoxic
Storm
Infection
Other acute medical illness
Acute emotional stress
Acute psychosis
Non thyroid surgery
Parturition
Trauma
Discontinuation of anti thyroid drug therapy
After radioiodine therapy
Post-thyroidectomy
After high-dose iodine administration
Iodinated radiographic contrast agents
RARE ASSOCIATIONS-
Vigorous palpation of thyroid gland
Subacute thyroiditis
Thyroxine over dosage (thyrotoxicosis factitia) Aspirin
intoxication
Hydatidiform mole
Organophosphate intoxication
Neurotoxins
Cytotoxic chemotherapy

7. History and Physical examination
H/O- fever, CVS (tachycardia, heart failure, arrhythmia
central nervous system (CNS) manifestations and GI symptoms (nausea,
vomiting, diarrhea, abdominal pain, intestinal obstruction, and acute hepatic
failure)
JTA , CNS involvement – POOR prognosis, increased mortality
Physical examination-high temperature, tachycardia, orbitopathy, goiter,
hand tremors, moist and warm skin, hyperreflexia, systolic hypertension, and
jaundice.
Investigations- TFT, CBC, LFT, RFT, Cortisol, Blood Glucose, Calcium levels
Imaging- Chest X ray, MRI Brain, ECG
*It is not necessary to have a very high level of thyroid hormone to cause
thyroid storm.

9. Burch Wartofsky Point Scale (BWPS)
THERMOREGULATORY
DYSFUNCTION
SCORE CARDIOVASCULAR DYSFUNCTION SCORE
99-99.9 F (37.2-37.7 C) 5 TACHYCARDIA
100-100.9 F (37.8-38.2 C) 10 99-109 BPM 5
101-101.9 F (38.3-38.8 C) 15 110-119 BPM 10
102-102.9 F (38.9-39.3 C) 20 120-129 BPM 15
103-103.9 F (39.4-39.9 C) 25 130-139 BPM 20
≥ 104 F (>40.0 C) 30 ≥ 140 BPM 25
CENTRAL NERVOUS SYSTEM SCORE CONGESTIVE HEART FAILURE SCORE
Agitation 10 Pedal Edema ( Mild) 5
Delirium/Psychosis/Lethargy 20 Bibasal Rales (Moderate) 10
Seizure/Coma 30 Pulmonary Edema (Severe) 15
GI-HEPATIC DYSFUNCTION SCORE Atrial fibrillation Present 10
Diarrhea,Nausea/Vomiting,Abdo
minal Pain
10 Precipitant History Present 10
Severe jaundice 20

10. INTERPRETATION-
• Thyroid storm highly likely >60
• Likely, 45–60
• Impending, 25–44
• unlikely, <25
• When it is not possible to distinguish a finding due to an intercurrent
illness from that of thyrotoxicosis, the higher point score is given so
as to favor empiric therapy
Reference-Burch HB, Wartofsky L. Life-threatening thyrotoxicosis:
thyroid storm. Endocrinol Metab Clin North Am 1993;22:263–277

11. The Japanese Thyroid Association (JTA)
Prerequisite for diagnosis
Presence of thyrotoxicosis with elevated levels of free triiodothyronine (FT3) or free thyroxine (FT4)
Symptoms
1. Central nervous system (CNS) manifestations: Restlessness, delirium, mental aberration/psychosis,
somnolence/lethargy, coma ( ≥1 on the Japan Coma Scale or ≤14 on the Glasgow Coma Scale)
2. Fever : ≥ 38˚C
3. Tachycardia : ≥ 130 beats per minute or heart rate ≥ 130 in atrial fibrillation
4. Congestive heart failure (CHF) : Pulmonary edema, moist rales over more than half of the lung field,
cardiogenic shock, or Class IV by the New York Heart Assciation or ≥ Class III in the Killip classification
5. Gastrointestinal (GI)/hepatic manifestations : nausea , vomiting, diarrhea, or a total bilirubin level ≥ 3.0
mg/dL

12. Diagnosis
Grade of TS Combinations of
features
Requirements for diagnosis
TS 1 First combination Thyrotoxicosis and at least one CNS manifestation
and fever, tachycardia, CHF, or GI/ hepatic
manifestations
TS 1 Alternate combination Thyrotoxicosis and at least three combinations of
fever, tachycardia, CHF, or GI/ hepatic
manifestations
TS 2 First combination Thyrotoxicosis and a combination of two of the
following: fever, tachycardia, CHF, or GI/hepatic
manifestations
TS 2 Alternate combination Patients who met the diagnosis of TS1 except that
serum FT3 or FT4 level are not available
TS1, “Definite” TS; TS2, “Suspected” TS.

13. Exclusion and provisions in JTA
Cases are excluded if other underlying diseases clearly causing any of
the following symptoms:
1.Fever (e.g., pneumonia and malignant hyperthermia
2.Impaired consciousness (e.g., psychiatric disorders and cerebrovascular disease)
3.Heart failure (e.g.acute myocardial infarction), and liver disorders (e.g., viral hepatitis and acute
liver failure).
• Difficult to determine whether the symptom is caused by TS or is
simply a manifestation of an undelying disease;
• Symptom should be regarded as being due to a TS that is caused by
these precipitating factors.
• Clinical judgment in this matter is required.

14. Comparing BWPS and JTA
1. BWPS of ≥ 45 or JTA Category TS 1 and TS 2 with e/o systemic decompensation require aggressive therapy
2. BWPS of 25-44, decision of aggressive therapy should be based on clinical judgment
3. JTA, TS 1 & TS 2 has tendency of underdiagnosis compared to BWPS ≥ 45
4. Similar rates of overdiagnosis with two systems
5. A BWPS of ≥ 45 is more sensitive than a JTA classification of TS1 or TS2 patients with a clinical diagnosis of
thyroid storm.
But for BWPS 25-44 use clinical judgement.

15. Management
1. Therapy to control increased adrenergic tone: Beta-blocker
2. Therapy to reduce thyroid hormone synthesis: Thionamide
3. Therapy to reduce the release of thyroid hormone: Iodine solution
4. Therapy to block peripheral conversion of T4 to T3: Iodinated
radiocontrast agent, glucocorticoid, PTU, propranolol
5. Therapy to reduce enterohepatic recycling of thyroid hormone: Bile
acid sequestrant

16. Management

17. • T4 is acted by the thyroidal type 1 and 2 deiodinases (D1 and D2) ,
this conversion is inhibited by PTU, that inhibits D1
• At synthesis level- ratio of T4 to T3 in human Tg is 15:1
• At secretion level- ratio of T4 to T3 in thyroid secretion is
approximately 10:1 ( catalyzed by D1 and D2)
• It is enhanced in Graves’ Disease, marked increase of the ratio of T3
to T4 production
• An inhibition of the D1-catalyzed T4 to T3 conversion may contribute
to the rapid effect of PTU to reduce circulating T3 in patients with
Graves disease

18. • Iodide inhibits the stimulation of thyroid adenylate cyclase by TSH
and by the stimulatory immunoglobulins of Graves disease.
• Increasing iodination of Tg also increases its resistance to hydrolysis
by acid proteases in the lysosomes

19. Thyrotoxic storm – Drugs and doses
DRUGS DOSING COMMENTS
Propyl thiouracil ( can be given IV) 500-1000 mg load then 250 mg
every 4 hourly
Blocks new hormone synthesis ( -
D1)
Methimazole 60-80 mg/day Blocks T4 to T3 conversion, (-) new
hormone synthesis
Propanolol 60-80 mg every 4 hours Consider invasive monitoring in congestive
heart failure patients, blocks T4 to T3
conversion in high doses
Alternate drug: esmolol infusion
Iodine ( saturated solution of
Potassium Iodide)
5 drops ( 0.25 ml or 250 mg) orally
every 6 hours
Do not start until 1 hr after ATD,
blocks new hormone synthesis and
release, alternate: Lugol’s iodine
Hydrocortisone 300 mg IV load then 100 mg every
8 hrs
May block T4 to T3 conversion,
prophylaxis against relative Adrenal
insufficiency, alternate-
dexamethasone

20. • Cholestyramine
• Plasmapheresis/ plasma exchange
• Emergency surgery
Carbimazole: Methimazole: PTU
C:M:P
40 mg : 30 mg : 400 mg
SSKI
Lugol solution
(Williams Textbook of Endocrinology, 14 th
edition)
38 mg/drop
6 mg/drop
1 drop = 0.05 ml
SSKI
Lugol solution
( 2016 ATA)
50 mg/drop
8 mg/drop

21. Management of Thyrotoxic storm
1.Reduction of thyroid hormone production and
secretion
Inhibition of T4 and T3 synthesis
• Propylthiouracil, methimazole Inhibition of T4 and T3
secretion
• Inorganic iodide (potassium iodide, Lugol solution)
• Radiographic contrast agents (sodium ipodate, iopanoic
acid)
• Lithium carbonate
• Thyroidectomy
2.Therapy directed against systemic disturbances
• Treatment of fever
• Acetaminophen
• External cooling
Correction of volume depletion and poor nutrition
• Intravenous fluid and electrolytes Glucose (calories)
Vitamins
• Supportive therapy Oxygen
• Vasopressor drugs
Treatment for congestive heart failure (diuretics, digoxin)
3.Amelioration of the peripheral actions of thyroid
hormone and Removal of T4 and T3 from serum-
• Inhibition of extra thyroidal conversion of T4 to T3 -PTU
• Radiographic contrast agents (sodium ipodate, iopanoic
acid)
• Glucocorticoids
• Propranolol or other β-adrenergic antagonist drugs
• Cholestyramine
• Plasmapheresis, hemodialysis, hemoperfusion
4.Treatment of any precipitating or underlying illness

22. Preparation of rectal formulations of
thionamides
Methimazole Propylthiouracil
Suppository-Dissolve 1200 mg methimazole in 12 mL
of water, and add to 52 mL cocoa butter containing 2
drops of polysorbate (Span) 80. Stir mixture to form
an emulsion, and pour into 2.6 mL suppository molds
to cool.
* Avoid phosphate-containing rectal preparations in
patients with kidney insufficiency or heart failure
Suppository-Dissolve 200 mg of propylthiouracil in a
polyethylene glycol base, and put into suppository
tablets
Retention enema-Dissolve 8 to 12 (50 mg) tablets of
propylthiouracil in 90 mL of sterile water.
OR
Dissolve 8 (50 mg) tablets of propylthiouracil in 60 mL
of mineral oil enema (eg, Fleet mineral oil) or in 60 mL
of sodium phosphates enema solution* (eg, Fleet
enema phospho-soda).
For either enema preparation: Administer by Foley
catheter inserted into the rectum, with balloon
inflated to prevent leakage for 2-hour retention.
1.Nabil N, Miner DJ, Amatruda JM. Methimazole: an alternative route of administration. J Clin Endocrinol Metab 1982; 54:180.
2.Walter RM Jr, Bartle WR. Rectal administration of propylthiouracil in the treatment of Graves' disease. Am J Med 1990; 88:69

24. Myxedema Coma
• Myxedema coma is a rare life-threatening clinical condition in
patients with longstanding severe untreated hypothyroidism, in
whom adaptive mechanisms fail to maintain homeostasis.
• First reported in 1879 by Ord from the St. Thomas Hospital, London.
• ≈ 200 cases have been reported subsequently
• Prognosis poor with a reported mortality between 20% and 50%.

27. Diagnosis and d/d
Three key features-
• Altered mental status
• Defective thermoregulation: hypothermia
• Precipitating event

28. Examination and Investigations
Physical Examination
• Hypothermia
• Hypoventilation
• Hypotension
• Bradycardia
• Dry coarse skin
• Macroglossia
• Delayed DTR
• Absence of mild diastolic hypertension in severely
hypothyroid patients is a warning sign of
impending myxedema coma.
Investigations
• Anemia
• Hyponatremia
• Hypoglycaemia
• Hypercholesterolemia
• High serum creatine kinase
• Low serum FT4 and high serum TSH (Serum TSH
can be low or normal)

29. Myxedema Coma: Precipitating and
Exacerbating Factors
1.Hypothermia
2.Infections
3.Cerebrovascular accidents
4.Congestive heart failure
5.Medications
6.Anesthetics
7.Sedatives
8.Tranquilizers
9.Narcotics
10.Amiodarone
11.Trauma
12.Gastrointestinal bleeding
13.Metabolic disturbances
exacerbating myxedema coma -
Hypoglycemia
Hyponatremia Hypoxemia
Hypercapnia Acidosis
Hypercalcemia

30. Diagnostic Scoring System for Myxedema Coma
Thermoregulatory Dysfunction
(Temperature, °C)
>35
32–35
<32
0
10
20
Precipitating Event
Absent
Present
0
10
Central Nervous System Effects
Absent
Somnolent/lethargic
Obtunded
Stupor
Coma/seizures
0
10
15
20
30
Cardiovascular Dysfunction
Bradycardia Absent
50-59
40–49
<40
Other EKG changes
Pericardial/pleural effusions
Pulmonary edema
Cardiomegaly
Hypotension
0
10
20
30
10
10
15
15
20
Gastrointestinal Findings
Anorexia/abdominalpain/constipation
Decreased intestinal motility
Paralytic ileus
5
15
20
Metabolic Disturbances
Hyponatremia
Hypoglycemia
Hypoxemia
Hypercarbia
Decrease in GFR
10
10
10
10
10

31. • ≥ 60 highly S/O or diagnostic of myxedema coma
• 25 to 59 S/O of risk for myxedema coma
• < 25 is unlikely to indicate myxedema coma
• ECG Changes- QT prolongation, low-voltage complexes, bundle branch
blocks, nonspecific ST- T changes or heart blocks.
Reference-Popoveniuc G, Chandra T, Sud A, et al. A diagnostic scoring
system for myxedema coma. Endocr Pract 2014;20:808–817

32. Management- Hypothyroidism
1.L4 alone-
A. Initial dose 300–500 mcg IV
B. Then 50–75mcgdaily IV or p.o. if conscious
C. Once stable, continue at 1.6mcg/kg while monitoring FT4 and TSH
2.L3 alone
A. Initial dose 30–50mcg IV
B. Follow with 10mcg q6h for next 24–48hr
C. Once conscious and taking oral medications ,switch to levothyroxine 75–100mcg daily
D. Continue at 1.6mcg/kg while monitoring FT4 and TSH levels
3.CombinationT4 PlusT3
A. Initial L4 dose 4mcg/kg lean bodyweight IV (≈200–250mcg) together with 20 mcg T3 IV.
B. Continue with T3 ,10mcg q8–12h
C. If still comatose on day2 (and day3)administer L4 100mcg IV
D. Once conscious and taking oral medications ,discontinue T3and continue T4 at 1.6mcg/kg while monitoring
FT4 and TSH levels

33. 2.Hypocortisolemia -Hydrocortisone , IV , 50 to 100 mg every 6 to 8 hours for several days, tapered then
stopped
3. Hypoventilation – esp those with morbid obesity, sedatives
4. Hypothermia – passive warming, blankets, core body temperature, electrical thermometers
5. Hyponatremia – cautious use of 3 percent saline ( Na < 120 mmol/L)with or without furosemide, NS
6. Hypotension – judicious use of iv fluid , 5-10 % dextrose in NS, hydrocortisone
7. Hypoglycemia – IV glucose
8. Precipitating event - vigorous search , Signs of infection (like fever, tachycardia, leukocytosis) may be
absent, prophylactic antibiotics

36. Take Home Message
• Rare conditions with high mortality
• High clinical suspicious
• Try all available options

37. THANK YOU